Trodelvy (sacituzumab govitecan-hziy)

Moreover, compared to sacituzumab govitecan, hIMB1636-LDP-AE showed more potent antitumor activity and significantly lower myelotoxicity in tumors with moderate Trop2 expression. This study fully revealed the potent antitumor efficacy of hIMB1636-LDP-AE, and also provided a new preparation method for LDM-based ADC, as well as a promising candidate for breast cancer and lung cancer therapeutics.

ADCs have advanced from hematologic to solid tumours, notably in breast cancer, and are now pivotal in metastatic urological cancers as both monotherapies and in combination regimens, underscored by the FDA's approval of enfortumab vedotin and sacituzumab govitecan for metastatic urothelial cancer. There is a continual search for agents in the metastatic, relapsed testicular cancer landscape. ADCs have emerged as a pivotal innovation in oncology, blending targeted antibody therapy with potent cytotoxic drugs, significantly advancing treatment options for urological malignancies.

In lung cancer, trastuzumab deruxtecan (T-DXd) is approved in human epidermal growth factor receptor 2 (HER2)-mutated, unresectable or metastatic non-small cell lung cancer, with ADCs targeting HER3 (patritumab deruxtecan), trophoblast cell-surface antigen 2 (datopotamab deruxtecan and sacituzumab govitecan [SG]) and mesenchymal-epithelial transition factor (telisotuzumab vedotin) in late-stage clinical development. In breast cancer, several agents are already approved and widely used, including trastuzumab emtansine, T-DXd and SG, and multiple late-stage trials are ongoing...The ETOP IBCSG Partners Foundation are driving strong collaborations in this field and promoting the generation/sharing of databases, repositories and registries to enable greater access data. This will allow the most important research questions to be identified and prioritised, which will ultimately accelerate progress and help to improve patient outcomes.

P1, N=20, Not yet recruiting, Henry Ford Health System | Initiation date: Feb 2024 --> Jun 2024

P1/2, N=56, Recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Not yet recruiting --> Recruiting

P2, N=110, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Apr 2027 --> Apr 2029 | Trial primary completion date: Apr 2024 --> Apr 2026

P2, N=18, Recruiting, Georgetown University | Not yet recruiting --> Recruiting

The observed response rate and safety of SG are consistent with the results of the ASCENT trial, with efficacy observed in patients with brain metastases, but observed PFS and OS are numerically shorter.

The results of this real-world analysis showed that both safety and efficacy of sacituzumab govitecan in mTNBC patients are consistent with that previously reported in regulatory trials. The use of premedication and supportive measures was associated with a satisfactory toxicity profile.

P=N/A, N=150, Recruiting, Fudan University

These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

The alternation of payload achieves different responses in different settings. T-Dxd followed by RC48 may be a potentially beneficial strategy in HER2-positive disease. Further research is needed to elucidate the mechanism of cross-resistance.

P1/2, N=75, Recruiting, Massachusetts General Hospital | Phase classification: P1b/2 --> P1/2 | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

Historically, trastuzumab emtansine (T-DM1) has been the most commonly used ADC for both early and metastatic HER2-positive disease. Considering the recent evidence related to trastuzumab deruxtecan (T-DXd), it is expected to assume the role of the main ADC in our clinical practice. Herein, we report a retrospective analysis of the sequence of different ADCs relying on available published data from clinical trials.

P1/2, N=143, Recruiting, Gilead Sciences | Trial primary completion date: Apr 2025 --> May 2026

P2, N=397, Recruiting, Gilead Sciences | Trial completion date: Jan 2028 --> Jan 2027

P2, N=120, Suspended, Vanderbilt-Ingram Cancer Center | Recruiting --> Suspended

P2, N=35, Not yet recruiting, National Taiwan University Hospital

P1/2, N=120, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

P2, N=30, Active, not recruiting, G1 Therapeutics, Inc. | Trial primary completion date: Jun 2023 --> Nov 2023

P2, N=50, Recruiting, Yale University | Trial primary completion date: Feb 2024 --> Dec 2024

P1/2, N=56, Not yet recruiting, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Initiation date: Dec 2023 --> Apr 2024

P2, N=500, Not yet recruiting, National Cancer Institute (NCI)

P2, N=40, Recruiting, Adrienne G. Waks | Initiation date: Apr 2024 --> Nov 2023

P1/2, N=54, Not yet recruiting, Icahn School of Medicine at Mount Sinai | Initiation date: Sep 2023 --> Mar 2024

P2, N=40, Recruiting, The University of Texas Health Science Center at San Antonio | Trial primary completion date: Feb 2024 --> Aug 2024

No abstract available

In the phase III TROPiCS-02 trial, intravenous sacituzumab govitecan demonstrated statistically significant and clinically meaningful improvements in progression-free survival and overall survival compared with physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) in adults with metastatic HR+/HER2- breast cancer. Sacituzumab govitecan demonstrated an overall benefit in terms of health-related quality of life. Current evidence indicates that sacituzumab govitecan is an effective treatment option, with a generally manageable tolerability profile, for patients with pre-treated, unresectable locally advanced or metastatic HR+/HER2- breast cancer.

In patients with HER2 negative MBC, two ADCs have FDA approval: sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd), both with topoisomerase-I (topo-I) inhibitor payloads. This is the first report describing emergence of TOP1 mutations under selective pressure from ADCs and the impact on mediating cross-resistance to ADC after ADC with topo-I inhibitor payloads. Novel ADCs with alternative payloads may potentially be more effective when used sequentially after an ADC with a topo-I inhibitor. Further biomarker research is needed to optimize ADC sequencing for patients with TOP1 mutant MBC.

P2, N=110, Active, not recruiting, Ana C Garrido-Castro, MD | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2025 --> Mar 2024

P2, N=348, Not yet recruiting, West German Study Group | Initiation date: Dec 2023 --> Apr 2024

Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Sacituzumab govitecan (SG), a first-in-class anti-trophoblast cell surface antigen 2 (Trop-2) antibody-drug conjugate, demonstrated superior efficacy over single-agent chemotherapy (treatment of physician's choice [TPC]) in patients with metastatic triple-negative breast cancer (mTNBC) in the international, multicenter, phase III ASCENT study.Patients were randomly assigned 1:1 to receive SG or TPC until unacceptable toxicity/progression...Overall, SG had a manageable safety profile, with ≤5% of treatment-related discontinuations because of adverse events and no treatment-related deaths. The safety profile was consistent across all subgroups.These data confirm the clinical benefit of SG over chemotherapy, reinforcing SG as an effective treatment option in patients with mTNBC in the second line or later.

P2, N=37, Recruiting, Chinese University of Hong Kong | Not yet recruiting --> Recruiting | Initiation date: Nov 2024 --> Feb 2024

SG plus carboplatin or cisplatin produced additive growth-inhibitory effects in vitro that trended towards synergy. These combinations were well tolerated by the animals. Combining SG with platinum-based chemotherapeutics demonstrates the benefit in these indications and warrants further clinical investigation.

P2, N=22, Recruiting, University of Kansas Medical Center | Not yet recruiting --> Recruiting

P3, N=603, Active, not recruiting, Gilead Sciences | Trial primary completion date: May 2024 --> Nov 2023

P3, N=170, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

P2, N=75, Not yet recruiting, Reshma L. Mahtani, D.O.

P2, N=37, Not yet recruiting, Chinese University of Hong Kong | Initiation date: Nov 2023 --> Nov 2024

P1/2, N=46, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Apr 2025 --> Oct 2025 | Trial primary completion date: Apr 2024 --> Oct 2024

P3, N=170, Suspended, National Cancer Institute (NCI) | N=465 --> 170

P1/2, N=675, Recruiting, Hoffmann-La Roche | N=470 --> 675 | Trial completion date: Nov 2026 --> Sep 2027 | Trial primary completion date: Aug 2025 --> Jun 2026